Gene variant boosts schizophrenia risk in already highly vulnerable teenagers

A study of adolescents who lack part of chromosome 22 could lead to identification of a gene suspected of a role in schizophrenia. Findings of that study appear in the November 2005 issue of Nature Neuroscience.

Although youths with the 22q11.2 chromosomal deletion syndrome already have a nearly 30-fold higher-than-normal risk of schizophrenia, those who have one of two common sequence versions of the suspect gene are more prone to cognitive decline, psychosis, and frontal-lobe tissue loss by late adolescence. The genetic variant appears to make symptoms of the deletion syndrome worse by chronically boosting the chemical messenger dopamine to an excessive level in the prefrontal cortex during development.

"It's not that there's a good or bad version of this gene," said National Institute of Mental Health (NIMH) Director Thomas Insel, MD. "Either version can be an accomplice, via interactions with other genes and environmental factors, in creating a dopamine imbalance that disturbs information processing."

Researchers followed 24 subjects with the deletion syndrome and 23 matched controlled subjects with a developmental disability. When first tested in childhood, subjects who had the syndrome and the met sequence (that is, the sequence that produces the amino acid methionine) did not suffer from psychotic disorders and performed cognitive tasks as well or better than subjects with the val sequence (i.e., produces the amino acid valine). But when those subjects were retested in late adolescence or early adulthood, seven (29.2%) had developed schizophrenia or another psychotic disorder, compared to only one from the group with developmental disabilities.

The conclusion? An increase in the level of dopamine that normally occurs during adolescence is further boosted in syndrome-affected teenagers who carry the met sequence--leading to "reduced efficiency of cognitive processing" during adolescence.

The study was funded by the funded by the National Institute of Health's (NIH), NIMH, and the National Institute on Child Health and Human Development.